Ribonucleotide reductase (RNR) catalyzes the reaction that produces 2′-deoxyribonucleotides from their corresponding ribonucleoside 5′-diphosphates. This reaction is a rate-limiting step in the pathway for the production of 2′-deoxyribonucleoside 5′-triphosphates, and it is necessary for DNA replication. Human RNR consists of two subunits, R1 and R2, and the expression of both proteins is required for enzymatic activity. R1 and R2 are encoded by different genes on separate chromosomes, and most importantly, their mRNAs are differentially expressed throughout the cell cycle. The R1 protein is stable through the entire cell cycle while R2 is only expressed during the late G1/early S phase when DNA replication occurs (Engstrom et al., 1985).
Inhibition of R2 has been an objective for anticancer and antiviral therapeutics. However, novel targeted inhibitors of R2 for treatment of cell proliferative disorders, such as cancer or pathogen infections, would be desirable.